Galvanic replacement reaction for in situ fabrication of litchi-shaped heterogeneous liquid metal-Au nano-composite for radio-photothermal cancer therapy
ABSTRACT: With tremendous research advances in biomedical application, liquid metals (LM) also offer fantastic chemistry for synthesis of novel nano-composites. Herein, as a pioneering trial, litchi-shaped heterogeneous eutectic gallium indium-Au nanoparticles (EGaIn-Au NPs), served as effective radiosensitizer and photothermal agent for radio-photothermal cancer therapy, have been successfully prepared using in situ interfacial galvanic replacement reaction. The enhanced photothermal conversion efficiency and boosted radio-sensitization effect could be achieved with the reduction of Au nanodots onto the eutectic gallium indium (EGaIn) NPs surface. Most importantly, the growth of tumor could be effectively inhibited under the combined radio-photothermal therapy mediated by EGaIn-Au NPs. Inspired by this approach, in situ interfacial galvanic replacement reaction may open a novel strategy to fabricate LM-based nano-composite with advanced multi-functionalities. Graphical abstract Image 1 Highlights • A facile method to synthesize heterogeneous liquid metal-Au nano-composite.• The galvanic replacement reaction mechanism is proposed for the first time.• The in situ growth of Au nanodots can improve radio-photothermal effect.• The enhanced radio-photothermal effect can effectively achieve cancer therapy.
Project description:Innovations in soft material synthesis and fabrication technologies have led to the development of integrated soft electronic devices. Such soft devices offer opportunities to interact with biological cells, mimicking their soft environment. However, existing fabrication technologies cannot create the submicron-scale, soft transducers needed for healthcare and medical applications involving single cells. This work presents a nanofabrication strategy to create submicron-scale, all-soft electronic devices based on eutectic gallium-indium alloy (EGaIn) using a hybrid method utilizing electron-beam lithography and soft lithography. The hybrid lithography process is applied to a biphasic structure, comprising a metallic adhesion layer coated with EGaIn, to create soft nano/microstructures embedded in elastomeric materials. Submicron-scale EGaIn thin-film patterning with feature sizes as small as 180?nm and 1??m line spacing was achieved, resulting in the highest resolution EGaIn patterning technique to date. The resulting soft and stretchable EGaIn patterns offer a currently unrivaled combination of resolution, electrical conductivity, and electronic/wiring density.
Project description:This paper describes the fabrication of soft, stretchable biophotovoltaic devices that generate photocurrent from photosystem I (PSI) complexes that are self-assembled onto Au electrodes with a preferred orientation. Charge is collected by the direct injection of electrons into the Au electrode and the transport of holes through a redox couple to liquid eutectic gallium-indium (EGaIn) electrodes that are confined to microfluidic pseudochannels by arrays of posts. The pseudochannels are defined in a single fabrication step that leverages the non-Newtonian rheology of EGaIn. This strategy is extended to the fabrication of reticulated electrodes that are inherently stretchable. A simple shadow evaporation technique is used to increase the surface area of the Au electrodes by a factor of approximately 10<sup>6</sup> compared to planar electrodes. The power conversion efficiency of the biophotovoltaic devices decreases over time, presumably as the PSI complexes denature and/or detach from the Au electrodes. However, by circulating a solution of active PSI complexes the devices self-regenerate by mass action/self-assembly. These devices leverage simple fabrication techniques to produce complex function and prove that photovoltaic devices comprising PSI can retain the ability to regenerate, one of the most important functions of photosynthetic organisms.
Project description:Liquid metals show unparalleled advantages in printable circuits, flexible wear, drug carriers, and electromagnetic shielding. However, the efficient and large-scale preparation of liquid metal nanodroplets (LM NDs) remains a significant challenge. Here, we propose a simple and efficient method for the large-scale preparation of stable eutectic gallium indium nanodroplets (EGaIn NDs). We compared different preparation methods and found that droplets with smaller particle sizes could quickly be produced using a shaking technique. The size of EGaIn NDs produced using this technique can reach 200 nm in 30 min and 100 nm in 240 min. Benefiting from the simple method, various surfactants can directly modify the surface of the EGaIn NDs to stabilize the prepared droplets. In addition, we discovered that shaking in an ice bath produced spherical nanodroplets, and after shaking for 30 min in a non-ice bath, rod-shaped gallium oxide hydroxide (GaOOH) appeared. Furthermore, the EGaIn NDs we produced have excellent stability-after storage at room temperature for 30 days, the particle size and morphology change little. The excellent stability of the produced EGaIn NDs provides a wider application of liquid metals in the fields of drug delivery, electromagnetic shielding, conductive inks, printed circuits, etc.
Project description:A method for accurately measuring the relative dielectric constant (ε<sub>r</sub>) of thin films of soft, organic materials is described. The effects of the bombardment of these materials with hot Al atoms, the most commonly used top electrode, are mitigated by using electrodes fabricated from eutectic gallium-indium (EGaIn). The geometry of the electrode is defined by injection into microchannels to form stable structures that are nondamaging and that conform to the topology of the organic thin film. The ε<sub>r</sub> of a series of references and new organic materials, polymers, and fullerene derivatives was derived from impedance spectroscopy measurements for both Al and EGaIn electrodes showing the specific limitations of Al with soft, organic materials and overcoming them with EGaIn to determine their dielectric properties and provide realistic values of ε<sub>r</sub>.
Project description:Breast cancer (BC) is the most frequently diagnosed cancer with a low survival rate and one of the major causes of cancer-related death. Methotrexate (MTX) is an anti-tumor drug used in the treatment of BC. Poor dispersion in water and toxic side effects limit its clinical application. Gold nanoparticles (AuNPs), owing to their specific structures and unique biological and physiochemical properties, have emerged as potential vehicles for tumor targeting, bioimaging and cancer therapy. An innovative nano drug-loading system (Au @PDA-PEG-MTX NPs) was prepared for targeted treatment of BC. Au @PDA-PEG-MTX NPs under near infra-red region (NIR) irradiation showed effective photothermal therapy against MDA-MB-231 human BC cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and generating excessive heat. In vivo studies revealed deep penetration ability of Au @PDA-PEG-MTX NPs under NIR irradiation to find application in cancer-targeted fluorescence imaging, and exhibited effective photothermal therapy against BC xenograft growth by inducing apoptosis. Histopathological analysis, cellular uptake, cytotoxicity assay, and apoptosis experiments indicated that Au @PDA-PEG-MTX NPs possessed a good therapeutic effect with high biocompatibility and fewer side effects. This Au NPs drug-loading system achieved specific targeting of MTX to BC cells by surface functionalisation, fluorescence imaging under laser irradiation, combined photothermal-chemotherapy, and pH- and NIR- triggered hierarchical drug release.
Project description:Eutectic gallium indium (EGaIn), a Ga-based liquid metal alloy holds great promise for designing next generation core-shell nanoparticles (CSNs). A shearing assisted ligand-stabilization method has shown promise as a synthetic method for these CSNs; however, determining the role of the ligand on stabilization demands an understanding of the surface chemistry of the ligand-nanoparticle interface. EGaIn CSNs have been created functionalized with aliphatic carboxylates of different chain length allowing a fundamental investigation on ligand stabilization of EGaIn CSNs. Raman and diffuse reflectance Fourier transform spectroscopies (DRIFTS) confirm reaction of the ligand with the oxide shell of the EGaIn nanoparticles. Changing the length of the alkyl chain in the aliphatic carboxylates (C2-C18) may influence the size and structural stability of EGaIn CSNs, which is easily monitored using atomic force microscopy (AFM). No matter how large the carboxylate ligand, there is no obvious effect on the size of the EGaIn CSNs, except the particle size got more uniform when coated with longer chain carboxylates. The AFM force distance (F-D) measurements are used to measure the stiffness of the carboxylate coated EGaIn CSN. In corroboration with DRIFTS analysis, the stiffness studies show that the alkyl chains undergo conformational changes upon compression.
Project description:Three techniques were compared for lowering the limit of detection (LOD) of the lateral flow immunoassay (LFIA) of the receptor-binding domain of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) based on the post-assay in situ enlargement of Au nanoparticles (Au NPs) on a test strip. Silver enhancement (growth of a silver layer over Au NPs-Au@Ag NPs) and gold enhancement (growth of a gold layer over Au NPs) techniques and the novel technique of galvanic replacement of Ag by Au in Au@Ag NPs causing the formation of Au@Ag-Au NPs were performed. All the enhancements were performed on-site after completion of the conventional LFIA and maintained equipment-free assay. The assays demonstrated lowering of LODs in the following rows: 488 pg/mL (conventional LFIA with Au NPs), 61 pg/mL (silver enhancement), 8 pg/mL (galvanic replacement), and 1 pg/mL (gold enhancement). Using gold enhancement as the optimal technique, the maximal dilution of inactivated SARS-CoV-2-containing samples increased 500 times. The developed LFIA provided highly sensitive and rapid (8 min) point-of-need testing.
Project description:Liquid metals are being studied intensively because of their potential as a drug delivery system. Eutectic gallium-indium (EGaIn) alloy liquid metals have a low melting point, low toxicity, and excellent tissue permeability. These properties may enable them to be vascular embolic agents that can be deformed by light or heat. In this study, we developed EGaIn particles that can deliver anticancer drugs to tumor cells in vitro and change their shapes in response to external stimuli. These particles were prepared by sonicating a solution containing EGaIn and amphiphilic lipids. The liquid metal (LM)/amphiphilic lipid (DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholin) particles formed a vehicle for doxorubicin, an anticancer drug, which was released (up to 50%) when the shape of the particles was deformed by light or heat treatment. LM/DSPC particles are non-toxic and LM/DSPC/doxorubicin particles have anticancer effects (resulting in a cell viability of less than 50%). LM/DSPC/doxorubicin particles were also able to mimic blood vessel embolisms by modifying their shape using precisely controlled light and heat in engineered microchannels. The purpose of this study was to examine the potential of EGaIn materials to treat tumor tissues that cannot be removed by surgery.
Project description:Gold nanoparticle-coated Pluronic-b-poly(L-lysine) nanoparticles (Pluronic-PLL@Au NPs) were synthesized via an easy one-step method and employed as carriers for the delivery of paclitaxel (PTX) in chemo-photothermal therapy, in which Pluronic-PLL acts as the reductant for the formation of AuNPs without the need for an additional reducing agent.The deposition of AuNPs on the surface of Pluronic-PLL micelles and the thermal response of the system were followed via ultraviolet-visible spectroscopy and dynamic light scattering. Calcein-AM and MTT assays were used to study the cell viability of MDA-MB-231 cells treated with PTX-loaded Pluronic-PLL@Au NPs, and we then irradiated the cells with NIR light.An obvious temperature response was observed for the Pluronic-PLL@Au NPs. Blood compatibility and in vitro cytotoxicity assays confirmed that the Pluronic-PLL@Au NPs have excellent biocompatibility. Compared to Taxol, the PTX-loaded Pluronic-PLL@Au NPs exhibited higher cytotoxicity in MDA-MB-231 cells. All of these results and confocal laser scanning microscopy analysis results suggest that Pluronic-PLL@Au NPs greatly enhance the cellular uptake efficiency of the drug.As confirmed by in vitro and in vivo studies, the combination of chemotherapy and photothermal therapy can cause more damage than chemo- or photothermal therapy did alone, demonstrating the synergistic effect of chemo-photothermal treatment. Thus, the as-prepared Pluronic-PLL@Au NPs are promising for chemo-photothermal therapy.
Project description:Stable suspensions of eutectic gallium indium (EGaIn) liquid metal nanoparticles form by probe-sonicating the metal in an aqueous solution. Positively-charged molecular or macromolecular surfactants in the solution, such as cetrimonium bromide or lysozyme, respectively, stabilize the suspension by interacting with the negative charges of the surface oxide that forms on the metal. The liquid metal breaks up into nanospheres <i>via</i> sonication, yet can transform into rods of gallium oxide monohydroxide (GaOOH) <i>via</i> moderate heating in solution either during or after sonication. Whereas heating typically drives phase transitions from solid to liquid (<i>via</i> melting), here heating drives the transformation of particles from liquid to solid <i>via</i> oxidation. Interestingly, indium nanoparticles form during the process of shape transformation due to the selective removal of gallium. This dealloying provides a mechanism to create indium nanoparticles at temperatures well below the melting point of indium. To demonstrate the versatility, we show that it is possible to shape transform and dealloy other alloys of gallium including ternary liquid metal alloys. Scanning transmission electron microscopy (STEM), energy-dispersive X-ray spectroscopy (EDS) mapping, and X-ray diffraction (XRD) confirm the dealloying and transformation mechanism.